The overall goal of this proposal is to better understand the basis of structural airway changes in severe asthma and how asthma exacerbations may contribute to their progression over time. The investigators propose to study a well-characterized cohort of adult and pediatric subjects with asthma using a multidisciplinary state-of-the-art approach. We hypothesize that severe asthma exacerbations, in some patients, are associated with incomplete recovery and activation of airway inflammatory cells in a regional distribution. The end result is a more permanent and less reversible airway obstruction that is a prominent feature of severe asthma.

Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.

Other Name: helium

Well controlled asthma

Subjects with well controlled asthma

Other: NC100182 Hyperpolarized 3He

Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.

Other Name: helium

Normal control

Subjects that are healthy normals

Other: NC100182 Hyperpolarized 3He

Magnetic Resonance Imaging (MRI) will take place and include inhalation of hyperpolarized helium to construct an image of the lungs.

Other Name: helium

Detailed Description:

We have shown that patients with severe asthma have heterogeneous regional ventilation defects and air trapping. Some of these defects are persistent, while others can be provoked with virus-induced exacerbations or bronchial challenge and recur in the same general areas on repeated challenge, suggesting localized airway dysfunction. In preliminary studies, inflammatory parameters tended to be more prominent in segments that showed ventilation defects on imaging. Therefore, we hypothesize that asthma exacerbations, in some patients, are associated with incomplete recovery and activation of airway inflammatory cells in a regional distribution. This leads to enhanced airway injury with airway dysfunction as reflected by ventilation defects and air trapping, and a more generalized increase in disease severity. To evaluate this hypothesis we propose the following specific aims: 1. To refine phenotyping of severe asthma using new variables from multiple domains in a large longitudinal patient cohort; and to determine the contribution of asthma exacerbations to disease progression. 2. To characterize regional obstructive patterns at baseline and their relationship to changes in pulmonary function; and to determine how incremental changes in regional airway dysfunction after asthma exacerbations may contribute to severe asthma. 3. To determine the contribution of established and novel biomarkers (YKL-40, vWF, & P-selectin), in refining the severe asthma phenotypes and the role of inflammatory cells in causing airway injury following virus-induced asthma exacerbations with subsequent development of ventilation defects.

Evidence that the participant or family may be unreliable or poorly adherent to their asthma treatment or study procedures,

Planning to relocate from the clinical center area before study completion, or

Any other criteria that place the subject at unnecessary risk according to the judgment of the Principal Investigator and/or attending physician(s) of record.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01760915